Artificial noise (AN), aiming to disturb the eavesdropper while avoiding the influence on the legitimate receiver, has arisen as an excellent technology for improving the physical-layer security of ...wireless communications. In order to challenge AN, zero-forcing elimination (ZFE) has been introduced as a possible countermeasure to mitigate the AN for the eavesdropper at the cost of more available receive antennas. In this contribution, from the perspective of eavesdroppers, we further conceive a class of efficient null-space elimination (NSE) schemes in order to reduce the number of receive antennas while enhancing the detection quality compared to original ZFE. Furthermore, the performance of secrecy rate as well as bit-error rate (BER) is quantified for both ZFE and NSE schemes through theoretical derivation, while the influence of imperfect channel state information (CSI) is also evaluated. The performance comparison of the above-mentioned schemes illustrates that NSE can provide more robust performance for eavesdroppers over ZFE, with lower hardware requirements as well as moderate complexity increase.
A highly efficient synthesis of enantioenriched spiroindolines by catalytic asymmetric dearomatization of indolyl dihydropyridines through a chiral phosphoric acid catalyzed enamine ...isomerization/spirocyclization/transfer hydrogenation sequence has been developed. This reaction proceeds under mild reaction conditions, affording novel spiroindolines in good yields (up to 88 %) with excellent enantioselectivity (up to 97 % ee). DFT calculations provide insights into the reaction mechanism as well as the origin of stereochemistry.
Born to be mild: An efficient synthesis of enantioenriched spiroindolines by catalytic asymmetric dearomatization of indolyl dihydropyridines through a chiral phosphoric acid (CPA)‐catalyzed enamine isomerization/spirocyclization/transfer hydrogenation sequence was developed (HEH=Hantzsch ester). The reaction proceeds under mild reaction conditions to afford spiroindolines in good yields (up to 88 %) with excellent enantioselectivity (up to 97 % ee).
In this paper, the terminal guidance problem of unpowered lifting reentry vehicle to stationary target is studied. Based on the requirement of attacking the target with high precision and high impact ...angle constraint, a fractional-order theory combined sliding mode guidance law is proposed. Its sliding surface is specially designed to satisfy the requirements in the terminal guidance phase. The novel fractional-order sliding mode guidance law is established in both two-dimensional environment and three-dimensional environment; then, the systems are proved to be asymptotically stable according to the Lyapunov stability principle. Finally, compared with the one without fractional-order term, experiments show the novel guidance law has better stability. Monte Carlo simulation verifies that the designed guidance law is more robust against the disturbance of random noise and ensures higher precision in terms of impact angle error and miss distance.
Background RC48-antibody-drug conjugates (ADC) link humanized anti-HER2 immunoglobulin with monomethyl auristatin E (MMAE). Clinical trials suggest promising antitumor activity in HER2-expressing ...solid tumors. This study probes RC48-ADC's efficacy and safety in patients with HER2-expressing advanced or metastatic solid tumors. Method Data was collected from 23 advanced cancer patients treated with RC48-ADC at our oncology center between July 2021 and December 2022. These patients exhibited at least 1 + expression of HER2 immunohistochemistry, had previously experienced at least one failed systemic chemotherapy, and were treated with RC48-ADC until the occurrence of intolerable adverse reactions or disease progression. The primary endpoint was the disease control rate (DCR), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Results 23 of 25 screened patients received RC48 treatment. The ORR was 43.5% (95% CI, 23.2-63.7%) with a median PFS of 6.0 months (95% CI, 4.8-7.4). In the low-to-medium HER2 expression subgroup, ORR was 37.5%, median PFS 5.75 months. In the high HER2 expression subgroup, ORR was 57.1%, median PFS 7 months. For the cohort combining RC48 with PD-1 inhibitors, ORR was 53.8%, median PFS 8 months. In the concurrent local radiation therapy subgroup, ORR was 40.0%, median PFS 6.0 months. Treatment-related adverse events (TRAEs) were anemia (60.8%), leukopenia (56.2%), raised transaminases (52.17%), and neutropenia (43.5%). Five patients (21.7%) experienced Grade 3 symptoms, including anemia (21.7%) and neutropenia (14.0%). No Grade 4 adverse reactions or deaths were reported. Conclusion RC48-ADC shows promising efficacy and manageable safety in HER2-expressing advanced or metastatic solid tumor patients. Keywords: RC48-ADC, HER2, Solid tumors, Disease control rate, Progression-free survival, Safety
Regiella insecticola is a bacterial endosymbiont in insects that exhibits a negative effect on the fitness of hosts. Thus, it is not clear why this costly endosymbiont can persist in host ...populations. Here, we tested a hypothesis that the infection pattern and negative roles of the endosymbiont were not constant but environmentally dependent. The grain aphids Sitobion avenae, belonging to different genotypes and infected with Regiella or not, were used in this study. We found that S. avenae populations were infected with Regiella, Hamiltonella defensa, Serratia symbiotica and Rickettsia. The predominant endosymbionts in the aphid populations varied with season. Serratia and Rickettsia were predominant from December to February while Regiella predominated from March to May. The vertical transmission of Regiella was poorer at high temperature, but following conditioning for seven generations, the transmission rate improved. Regiella inhibited the production of winged aphids at 25 °C, but it did not affect winged morph production at the higher temperatures of 28 °C and 31 °C. Regiella infection decreased the intrinsic rate of increase (r
) of aphids at 25 °C and 28 °C. However, at 31 °C, the effect of Regiella on the r
varied depending on the aphid genotype and density. Thus, the negative effects of this endosymbiont on its host were environmentally dependent.
In this contribution, we investigate reconfigurable intelligent surface assisted space-time line code (RIS-STLC) transmission for enhancing the signal quality when the direct link between the ...transmitter and receiver is blocked. In the context of intelligent transmission by RIS, the concept of index modulation (IM) is integrated into the pursuit of higher spectral efficiency, while a two-step detection is developed to improve the performance. Correspondingly, for blind transmission where the channel information at RIS is not available, the phase at RIS not associated with the channel is considered. Subsequently, the bit-error-rate (BER) performances of the proposed RIS-STLC system conditioned on both the intelligent and blind transmission are quantified. Theoretical analysis and simulation results demonstrate the effectiveness of the development of RIS-STLC.
Abstract Acinar metaplasia is an initial step in a series of events that can lead to pancreatic cancer. Here we perform single-cell RNA-sequencing of mouse pancreas during the progression from ...preinvasive stages to tumor formation. Using a reporter gene, we identify metaplastic cells that originated from acinar cells and express two transcription factors, Onecut2 and Foxq1. Further analyses of metaplastic acinar cell heterogeneity define six acinar metaplastic cell types and states, including stomach-specific cell types. Localization of metaplastic cell types and mixture of different metaplastic cell types in the same pre-malignant lesion is shown. Finally, single-cell transcriptome analyses of tumor-associated stromal, immune, endothelial and fibroblast cells identify signals that may support tumor development, as well as the recruitment and education of immune cells. Our findings are consistent with the early, premalignant formation of an immunosuppressive environment mediated by interactions between acinar metaplastic cells and other cells in the microenvironment.
As an aerial base station, unmanned aerial vehicle (UAV) has been considered as a promising technology to assist future wireless communications due to its flexible, swift and low cost features, where ...resource allocation is the basis for ensuring energy-efficient UAV-assisted networks. This paper formulates a joint optimization problem of user association, UAV trajectory design and power control to maximize the channel capacity among all ground users at a limited power level in a downlink transmission. To tackle the mixed-integer non-linear programming problem, this paper proposes a clustering-aided reinforcement learning approach consisting of three consecutive stages. Firstly, modified expectation-maximization unsupervised learning algorithm is investigated to cluster the ground users, which reduces the dimensions and hence, the association complexity is reduced as well. Then, Kuhn-Munkres algorithm is incorporated for user association, which associates a UAV with the ground users via matching to the cluster, and assigns the UAVs to the centroid of the matching cluster for pre-placement, with the aim of speeding up the convergence of the following deep reinforcement learning algorithm. Finally, a multi-agent twin delayed deep deterministic (MATD3) policy gradient is proposed to solve the non-convex sub-problem, which determines the transmit power and designs the fine-tuned trajectory of UAVs. By incorporating low-bias value estimation technique, the reward of the proposed MATD3 algorithm is improved. Simulation results have demonstrated that our proposed approach achieves higher reward as well as converging faster than existing reinforcement algorithms. Besides, the clustering-aided reinforcement learning has lower computational complexity than the benchmark schemes.
Despite the diverse etiologies of drug-induced liver injury (DILI), innate immunity activation is a common feature involved in DILI progression. However, the involvement of innate immunity regulation ...in inflammation resolution and liver regeneration in DILI remains obscure. Herein, we identified the chemokine CCL5 as a central mediator of innate immunity regulation in the pathogenesis of DILI. First, we showed that serum and hepatic CCL5 levels are elevated in both DILI patients and an APAP-induced liver injury (AILI) mouse model. Interestingly, both nonparenchymal cells and stressed hepatocytes are cell sources of CCL5 induction in response to liver injury. Functional experiments showed that CCL5 deficiency has no effect on the early phase of AILI but promotes liver repair in the late phase mainly by promoting inflammation resolution and liver regeneration, which are associated with an increased number of hepatic M2 macrophages. Mechanistically, CCL5 can directly activate M1 polarization and impede M2 polarization through the CCR1- and CCR5-mediated activation of the MAPK and NF-κB pathways. We then showed that CCL5 inhibition mediated by either a CCL5-neutralizing antibody or the antagonist Met-CCL5 can greatly alleviate liver injury and improve survival in an AILI mouse model. Our data demonstrate CCL5 induction during DILI, identify CCL5 as a novel innate immunity regulator in macrophage polarization, and suggest that CCL5 blockage is a promising therapeutic strategy for the treatment of DILI.
Recently, communications with the aid of reconfigurable intelligent surface (RIS), which operates with the aim of enhancing the system communication performance, have aroused extensive researches. ...Furthermore, the use of RIS for positioning has been considered. Therefore, we focus on a practical structure of indoor positioning assisted by distributed RISs through utilizing their ability to manipulate multipath signals, through the developed quasi-static and dynamic modes. Specifically, in the quasi-static mode, for reducing the implementation cost, the reflection coefficients for each RIS are preset and remain constant. In the dynamic mode, the reflection coefficients can be timely updated with a two-step positioning approach toward more accurate positioning performance. Furthermore, the Cramér-Rao lower bound of the developed positioning scheme is quantified through theoretical analysis. Both theoretical analysis and simulation results demonstrate that RIS has the potential to realize accurate positioning even with a single access point, due to its ability to mark the channel and replace traditional active positioning anchors. Meanwhile, we also show that the developed two-step positioning scheme can achieve considerable performance gain in accurate positioning.
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